1. Field of the Invention
The present invention relates to a novel process for de-monoarylmethylation or de-diarylmethylation which comprises treating a .beta.-lactam derivative having a mono- or diarylmethyl group on the nitrogen atom of the .beta.-lactam ring with an acid or ceric ammonium nitrate to convert the N-substituent into a hydrogen atom; to some novel substances among the starting materials used in the above process and the desired products having an antibacterial activity; to .beta.-lactam derivatives among the starting materials used in the process which are useful as intermediates for the synthesis of pharmaceutical agents; and to a process for the preparation thereof.
2. Description of the Prior Art
Heretofore, as a method to remove a monoarylmethyl group, e.g., 2,4-dimethoxybenzyl, substituted at the nitrogen atom of the .beta.-lactam ring, an oxidative cleavage using potassium persulfate has been known (J.A.C.S., 99, 2352 (1977)). However, this method has various disadvantages in yield and operation, for example, it requires a relatively high reaction temperature, it cannot be applied to unstable compounds, it requires an oxidizing agent and thus use of compounds having groups susceptible to oxidative conditions provides complicated products, and it requires reaction in a buffering solution in order to prevent the ring cleavage of the .beta.-lactam ring and so forth.
As a result of extensive studies in pursuit of a novel process to remove a mono- or diarylmethyl group from the nitrogen atom of the .beta.-lactam ring which is more useful, easier to handle or applicable more widely, the present inventors found that, by treating with an acid or ceric ammonium nitrate, the reaction proceeds under milder conditions than by the conventional method which employs potassium persulfate with more simplified operation and gives a desired product at a higher yield. Although several processes for producing .beta.-lactam antibacterial substances have hitherto been known, each of these conventional processes had several drawbacks which made them infeasible for production in a large quantity. For instance, a typical process which has been used frequently comprises forming a .beta.-lactam derivative having a nitrogen atom substituted at the .alpha.- position of the .beta.-lactam ring by reacting an azidoacetic acid derivative with a Schiff base, but this process was not easily applied to the production on an industrial scale because the use of the azido derivative is dangerous during handling. More recently, A. K. Bose et al have proposed a process for producing a compound of the formula (A): ##STR1## and further a process for producing bicyclic .beta.-lactam derivatives of the formulae (B) and (C): ##STR2## which have strong antibacterial activity and are therefore useful as medicines by converting the substituent on the nitrogen atom of the compound (A) into a hydrogen atom via several subsequent steps (Tetrahedron Letters, 2771 (1979)). The process proposed for the production of the compound (A) comprises reacting a Schiff base derived from veratrylamine and cinnamaldehyde with an (.alpha.-methyl-.beta.-alkoxycarbonyl)vinylaminoacetic acid in the presence of a chloroformate ester and triethylamine. However, since its reaction yield is low, and the compound (A) is obtained as an oil and is reported to be isolated and purified by a silica gel chromatography, this compound (A) and its production process still have many problems to be solved in order to be applied on a commercial scale.
Under such situations, we have conducted further studies based on the process by A. K. Bose et al. in order to obtain novel single .beta.-lactam derivatives useful as key intermediates for producing known or novel .beta.-lactam derivatives superior to the compound (A), by improving the above described drawbacks to make mass production feasible.